Atorvastatin having the following structural formula is an inhibitor of HMG-CoA reductase (3-hydroxy-3-methylglutaryl-coenzyme A reductase) and is known as an effective therapeutic agent for hyperlipidemia, hypercholesterolemia, arteriosclerosis, osteoporosis, benign prostatic hyperplasia and Alzheimer's disease:

U.S. Pat. Nos. 4,681,893 and 5,273,995 discloses, as atorvastatin, lactone forms of trans (±)-5-(4-fluorophenyl)-2-(1-methylethyl)-N,4-diphenyl-1-[(2-tetrahydro-4-hydroxy-6-oxo-2H-pyran-2-yl)ethyl]-1H-pyrrole-3-carboxamide, and amorphous forms of [R—(R*,R*)]-2-(4-fluorophenyl)-β,δ-dihydroxy-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1H-pyrrole-1-heptanoic acid and its calcium salts.
Various methods for preparing atorvastatin and methods for preparing an important intermediate of atorvastatin are disclosed in U.S. Pat. Nos. 5,003,080, 5,097,045, 5,124,482, 5,149,837, 5,155,251, 5,216,174, 5,245,047, 5,273,995, 5,397,792 and 5,342,952. Such amorphous forms are unstable to heat, light, oxygen and moisture, and thus the storage conditions thereof are limited. Also, such amorphous forms are unsuitable for the filtration and drying of products in mass production.
The crystalline polymorphic form of atorvastatin hemi-calcium salt is disclosed in U.S. Pat. Nos. 5,969,156 and 6,121,461 and International Patent Publication Nos. WO 01/36384, WO 02/43732, WO 03/070702 and WO 03/004470.
The atorvastatin hemi-calcium salt may be formulated into forms for oral administration, such as tablets, capsules, lozenges and powders. Thus, there is a need to produce atorvastatin in a pure and crystalline form to enable formulations to meet exacting pharmaceutical requirements and specifications. Accordingly, a crystalline form of atorvastatin that is more stable and easy to produce in large amounts is required in the art.